Because host susceptibility to the Friend virus (FV) complex is a multiple-gene trait, the leukemic disease induced by FV may become an excellent experimental model for human leukemia. Three major resistance genes, H-2, Fv-1 and Fv-2, have been identified and located in the mouse genome, but the precise mechanisms by which they act remain unknown. We propose here to examine the Fv-2 resistance gene in considerable detail, and to identify and characterize other host resistance genes to both N-tropic and B-tropic strains of FV. In addition, we plan to study the components of the FV complex: the defective spleen focus-forming virus (SFFV) with a new tissue culture assay, and its helper virus, and the manner by which its host range may become NB-tropic. A basic tool of the proposed studies will be the congenic D2. Fv-2r strain, soon to be completed, which differs from DBA/2 only with respect to the FV-2 locus. Comparisons of DBA/2 and D2/Fv-2r will be performed in order to determine their capacity to replicate FV, their production of tumor colony-forming cells, their capacity to support the colonial growth of these cells in the spleen and in the bone marrow, their susceptibility to transformation by FV in a culture system, and other hematological parameters. Other tools in this proposal are the spleen focus assay and the tumor colony assay; the first measures FV in a preparation by its capacity to induce foci of transformed cells in susceptibility mice, whereas the second measures FV-transformed donor cells by the formation of tumor colonies in the spleens of virus-resistant mice.